An acute injection of ascorbic acid (120mg/kg, i.p.) or chronic treatment with isoproterenol (4 microgram/kg, l.m., 3 times a day for 7 days) reduced airway sensitivity in guinea pigs to histamine and isoproterenol by 4-fold. Treatments also abolished the effects of beta-adrenergic blockade with propranolol (10mg/kg, i.p.). Sensitivities to histamine, isoproterenol and propranolol were restored to control values after a single injection of indomethacin (30mg/kg, i.p.). Membrane fractions, prepared from bronchial tissues and which sedimented between 280 g and 100,000 g, showed a high affinity for the radio ligand, 125I hydroxybenzylpindolol. 90% of the binding was displaced by 1-propranolol (EC50 value 10 minus to the 8th power M). D-propranolol was less effective in this regard (EC50 value 10 to the minus 6th power M). Phentolamine (up to 10 to the minus 3rd power M) and phenoxybenzamine (up to 10 to the minus 5th power M) displaced less than 10% of the bound pindolol. In animals chronically treated with isoproterenol, the specific binding was reduced by 50%. The membrane fractions also showed adenylate cyclase activity 8pM cyclic AMP/minute/mg protein in 2mM Mg 2 ion and 40pM cyclic AMP/minute/mg protein in 10mM Mg 2 ion. The stimulation by magnesium was reduced (50%) after chronic isoproterenol treatment. Prostaglandin production by airway smooth muscle is increased after ascorbic acid or isoproterenol treatments. Our data suggest a relationship between the loss of adrenergic binding sites and prostaglandin production.